Acute Life-Threatening Contrast Induced Thrombocytopenia Following Diagnostic Coro- nary Angiography: A Case Report and Literature Review

Acute severe thrombocytopenia following contrast administration is incredibly rare, but it can lead to significant morbidity. This case details the experience of a 63-year-old male whose diagnostic coronary angiography quickly led to severe thrombocytopenia with cardiovascular compromise in the absence of any immediate symptoms of anaphylaxis. His platelet count normalized within a week, increasing from 2 × 103/μL to 328 × 103/μL. A thorough review of the literature along with the present case is being reported.

P2Y12 inhibitor was given before or during the procedure. Coronary angiography showed three-vessel disease with a Fractional Flow Reserve (FFR) positive Right Coronary Artery (RCA) lesion; Percutaneous Coronary Intervention (PCI) was deferred in favor of a potential Coronary Artery Bypass Graft (CABG). Intraoperative hypotension was attributed to nitroglycerin and adenosine rather than anaphylaxis since it was not associated with other symptoms including dyspnea, throat tightness, pruritis or flush. Vascade vascular closure system (Cardiva Medical, Inc.) was used along with ten minutes of manual pressure. Good hemostasis at the access site was achieved.
However, within two hours of the procedure, femoral access site was found to develop a large hematoma complicated by hypotension and supraventricular tachycardia. Resuscitation was done with intravenous normal saline and twenty-five minutes of direct manual pressure applied to the access site. A FemoStop® plus compression system was then placed. Intravenous vasopressors and amiodarone were initiated to stabilize the condition.
Patient was emergently taken to the catheterization lab for a right iliac and femoral angiogram via contralateral access using an additional 40mL of visipaque which ruled out retroperitoneal hemorrhage. Mild access site active extravasation was noted. Decision was made to perform prolonged manual compression which eventually achieved hemostasis. Immediately afterwards, he was found to have platelets of 2 × 10 3 . Peripheral smear confirmed thrombocytopenia and identified rare schistocytes. Doppler studies of all four extremities were preformed to rule out Deep Venous Thrombosis (DVT). Normal INR/

Introduction
Severe thrombocytopenia following contrast administration is a rare phenomenon. As per our literature search derived from PubMed, there have been a net fourteen reported cases of acute, severe thrombocytopenia following contrast administration. Due to rarity of this phenomenon, a drastic drop in platelet counts is not anticipated, which could be disastrous in the context of recent femoral access. Platelet count usually responds well to conservative therapy and spontaneously returns to normal within a week.
The patient described here presented for an elective left heart catheterization complicated by severe thrombocytopenia two hours post-procedure leading to a large inguinal hematoma at the access site and life-threatening hemodynamic compromise requiring vasopressors.

Case Report
A male patient aged 63 years with a history of atrial flutter, smoking and hypertension was referred for a left heart catheterization for further evaluation following abnormal myocardial perfusion stress test. He had no prior cardiac procedures, known drug allergies or contrast exposures. On the day of the procedure, he presented with normal vital signs and a platelet count of 269 × 10 3 . 6-Fr access was obtained in the right common femoral artery. During the coronary angiography, the patient received intracoronary (IC) adenosine and nitroglycerin, unfractionated heparin (intra-arterial), intravenous fentanyl, midazolam, phenylephrine and 100mL of Visipaque-320, a non-ionic iso-osmolar contrast medium. Neither Aspirin nor a Open Access Journal cases closely resemble the thrombocytopenia induced by Ligand-Mimetic Fibrinogen receptor antagonists (GpIIb-IIIa inhibitors) [5]. Thrombocytopenia associated with GpIIb-IIIa inhibitors is a wellknown phenomenon where a severe, acute drop in platelet counts occurs within hours of exposure followed by recovery within a week. This can be associated with fever, chills and other systemic symptoms. These antibodies can be naturally occurring, accounting for the observation that platelet destruction can occur within a few hours of the first exposure to one of these medications [6,7].

Sci Forschen
Maintaining a high clinical suspicion for contrast induced thrombocytopenia is paramount. Thrombocytopenia can be the only manifestation; however, systemic symptoms like fever, chills and hemodynamic instability have been reported. Avoidance of the contrast exposure especially in close temporal proximity with the earlier exposure is of utmost importance. Once established, sensitivity to contrast causing immune thrombocytopenia is usually permanent; hence, patients should avoid future exposure [7]. Glucocorticoids use is controversial, but often administered. It is difficult to attribute the improvement in platelet count to steroid administration as this could be simply due to withdrawal of the sensitizing agent itself. IV immunoglobulin's and plasma exchange are used for other forms of drug induced thrombocytopenia; however, in the context of contrast induced thrombocytopenia, we found only one reported case of IV immunoglobulin's [4] while none reported use of plasma exchange. Platelet counts invariably improved within next one to two weeks, regardless of the treatment options.

Conclusion
Contrast induced thrombocytopenia is rare but clinically important entity especially in a busy cardiovascular practice. Awareness of this phenomenon is paramount in avoiding future contrast exposures and management of the patient. Platelet count invariably improve within days, however, supportive care during this interval is critical.
PTT, LDH and fibrinogen ruled out DIC. A second peripheral smear found no schistocytes and identified only a single platelet in addition to increased eosinophils. HIT (Heparin Induced Thrombocytopenia) antibodies were negative. Indirect antibodies to platelets detected by flow cytometry were positive. Provisional diagnosis of contrast induced thrombocytopenia was made.
The patient ultimately received four units of platelets and two units of packed RBCs. He had melena for next 48 hours which, on colonoscopy, were found to be due to diffuse mucosal bleeding. This complication was likely due to the severe thrombocytopenia as no focal spot of gastrointestinal hemorrhage was found on esophagogastroduodenoscopy or colonoscopy.
Although a few case reports [1][2][3] have documented corticosteroid administration in similar situations, there is insufficient literature to support this intervention. Hence, we decided not to use IV corticosteroids. Platelet counts increased to 127 × 10 3 by discharge three days later and were 328 × 10 3 in one week. Due to prompt improvement in platelet count, marked improvement in patient's clinical condition and logistic constraints, allergy specialist was not involved in the case.
Patient subsequently underwent successful three-vessel CABG and was reportedly event free since the last clinical encounter. Temporal trend of platelet count is represented in figure 1.

Discussion
There are fourteen reported cases of acute, severe thrombocytopenia following contrast administration as per our literature search derived from PubMed (Table 1). Both ionic and non-ionic, low and high osmolar contrast agents have been reported to be associated with this phenomenon. Repeat exposure within weeks of the primary exposure were invariably associated with recurrent thrombocytopenia [1,2,4].
Clinical profile, temporal trend of platelet reduction and recovery noted in these handful of contrast-induced thrombocytopenia

Time to Recovery (days)/platelet count (× 10 3 /μL)
Park M, et al. [3] 63-year-old male with chronic alcohol intake underwent CT Liver with contrast for assessment of abnormal liver function test. Patient presented to the emergency room 6 hours after discharge with hematoma around the IV site and stable vital signs. No anaphylaxis signs.

May-64
Ferreira RM, et al. [8] 71-year-old woman underwent elective PCI to LAD. 5 hours after exposure, she developed chills, nausea, vomiting along with bleeding from the femoral access site.

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Garcia Bueno MJ, et al. [7] 65-year-old woman underwent whole body CT scan with contrast. 12 hours later, she presented to emergency department with headache, fever, vomiting, diffuse petechia, ecchymoses and gingival bleeding. Previous episodes of contrast exposure were associated with chills and fever; however, no bleeding was noted.   Saitoh T, et al. [11] 70-year-old man who presented with hemiparesis underwent CT head with contrast. 3 hours later, he developed purpura and his platelets dropped to 5 (× 10 3 /μL).

5
Iopamidol (nonionic), 100 cc IV corticosteroids and platelet transfusions; negative anti-PF4 antibody; platelet aggregation seen on in vitro contrast exposure to the patient's whole blood.

days
Wiemer M, et al. [4] 66-year-old woman with unstable angina underwent coronary angiography. 8 hours later platelet counts dropped from 310 to 1 (× 10 3 /μL). This was complicated by access site hematoma and renal failure requiring hemodialysis. Three weeks later, she underwent another angioplasty and had a similar drop in platelets. Lacy J, et al. [15] 79-year-old male with diabetes and aortic stenosis underwent cardiac catheterization. Immediately after procedure, he experienced chills, fever and hypotension. Within 8 hours, his platelets were 30 × 103 and dropped to 2 × 103 by the next day.